Carnitine/xenobiotics transporters in the human mammary gland epithelia, MCF12A.

The barrier function of the human mammary gland collapses if challenged with cationic drugs, causing their accumulation in milk. However, underlying molecular mechanisms are not well understood. To gain insight into the mechanism, we characterized transport of organic cations in the MCF12A human mammary gland epithelial cells, using carnitine and tetraethylammonium (TEA) as representative nutrient and xenobiotics probes, respectively. Our results show that the mammary gland cells express mRNA and proteins of human (h) novel organic cation transporters (OCTN) 1 and hOCTN2 (a Na+-dependent carnitine carrier with Na+-independent xenobiotics transport function), which belong to the solute carrier superfamily (SLC) of transporters. Other SLC OCTs such as hOCT1 and extraneuronal monoamine transporter (EMT)/hOCT3 are also expressed at mRNA levels, but hOCT2 was undetectable. We further showed mRNA expression of ATB0+ (an amino acid transporter with a Na+/Cl(-)-dependent carnitine transport activity), and Fly-like putative transporter 2/OCT6 (a splice variant of carnitine transporter 2: a testis-specific Na+-dependent carnitine transporter). TEA uptake was pH dependent. Carnitine uptake was dependent on Na+, and partly on Cl-, compatible with hOCTN2 and ATB0+ function. Modeling analyses predicted multiplicity of the uptake mechanisms with the high-affinity systems characterized by K(m) of 5.1 microM for carnitine and 1.6 mM for TEA, apparently similar to the reported hOCTN2 parameter for carnitine, and that of EMT/hOCT3 for TEA. Verapamil, cimetidine, carbamazepine, quinidine, and desipramine inhibited the carnitine uptake but required supratherapeutic concentrations, suggesting robustness of the carnitine uptake systems against xenobiotic challenge. Our findings suggest functional roles of a network of multiple SLC organic cation/nutrient transporters in human mammary gland drug transfer.

Bilateral tubal pregnancies after the termination of intrauterine pregnancy following gamete intrafallopian transfer.

It is well known that the prevalence of heterotopic pregnancies following assisted reproductive technology (ART) is much higher than among spontaneous pregnancies. Here, we illustrate a very rare case of bilateral simultaneous tubal pregnancies combined with intrauterine pregnancy (incomplete abortion) following gamete intrafallopian transfer (GIFT). In this case, unsuspected bilateral tubal pregnancies were diagnosed when laparotomy was performed 10 days after the termination of an intrauterine pregnancy. We conclude that a careful monitoring after the termination of an intrauterine pregnancy should be performed when the patient has prolonged genital bleeding, which might be a warning signal of heterotopic pregnancy existence even in patients without any risk factors of ectopic pregnancy. (Reprod Med Biol 2002; 1: 65-67).